Bordetella bronchiseptica (B. bronchiseptica) is a highly infectious Gram-negative bacterium that can efficiently colonize healthy ciliated respiratory mucosa to cause respiratory infections in a wide range of host species. Accordingly, B. bronchiseptica is an etiologic agent in both atrophic rhinitis in pigs and kennel cough in dogs.
Notably however, humans are far more likely to be infected by the better known Bordetella pertussis (B. pertussis) for which humans are the only natural target [see, Stevenson and Roberts, FEMS Immunology and Medical Microbiology 37:121-128 (2003)]. In addition, unlike B. pertussis, B. bronchiseptica does not express the pertussis toxin. Furthermore, whereas B. pertussis infections are not known to result in prolonged colonization in the upper respiratory tract, B. bronchiseptica causes chronic infection in the upper respiratory tract in a number of different animal species. Consistently, whereas the systemic administration of a live B. pertussis vaccine recently has been proposed for human subjects [see, U.S. Publication No. 2009/0246222 A1], heretofore, live attenuated B. bronchiseptica vaccines have been designed for local intra-nasal administration into non-human animals, e.g., Nobivac®KC and Intra-Trac II (available from Merck Animal Health), Recombitek® KC2 (available from Merial) and Bronchi-Shield III (available from Fort Dodge).
One particular way to generate a live attenuated bacterium is to modify one or more key genes of that bacterium. In many microorganisms chorismate is a critical intermediate in the biosynthesis of important aromatic compounds, including folic acid and the three aromatic amino acids, phenylalanine, tyrosine, and tryptophan [Moat et al., Microbial Physiology (2002) Wiley-Liss, Chapter 15, pgs. 525-527]. Therefore, inactivation of a gene within the biosynthetic pathway of chorismate, such as aroA, has been used to generate live attenuated bacteria. Accordingly, a significant number of bacteria have been constructed to contain a deletion in their aroA genes including: Mannheimia haemolytica, Pasteurella multocida, Hemophilus somnus [see, e.g., Briggs, and Tatum, Applied and Environmental Microbiology, 71(11) 7187-7195 (2005); Tatum and Briggs, Applied and Environmental Microbiology, 71 (11) 7196-7202. (2005); U.S. Pat. No. 5,840,556], Salmonella typhimurium [Dougan et al., Molecular and General Genetics, 207(2-3) 402-405 (1987), and B. pertussis [Roberts et al., Infectious Immunology 58:732-739 (1990)]. However, heretofore, vaccines containing such aroA mutant bacteria have, for the most part, shown minimal if any success, see e.g., paragraph [0133] of U.S. Publication No. 2009/0246222 A1, which specifically refers to the rather limited success of vaccines comprising B. pertussis with an aroA deletion, and which strongly recommends instead the use of avirulent, live B. pertussis constructs with a mutation within a gene encoding one of the three major toxins of B. pertussis. 
An aroA deletant strain of B. bronchiseptica also has been constructed [Stevenson and Roberts, Vaccine 20, 2325-2335 (2002)]. These workers employed their deletant aroA B. bronchiseptica strain solely in an intranasal vaccine. Intranasal vaccines however, are inconvenient to administer, especially to adult animals, such as canines or felines that often resist administration of any substance into their nostrils. Administering such intranasal vaccines also creates a risk that the amount of vaccine taken in by the animal will be significantly less than the dose shown to be protective, should the animal sneeze during the administration. On the other hand, heretofore, systemic administration of live vaccines has not been regarded as a safe option, since it is known that the systemic administration of live B. bronchiseptica, even when attenuated, can lead to serious abscess formation [see e.g., Toshach et al., J Am Anim Hosp Assoc 33:126-128 (1997)].
Several killed whole cell and sub-unit B. bronchiseptica vaccines also have been described for parenteral administration to dogs, including the killed whole cell B. bronchiseptica vaccine Bronchicine® CAe, which is available from Pfizer Animal Health. Unfortunately, there also are several disadvantages to such killed B. bronchiseptica vaccines. For example, lipopolysaccharides (LPS) are inherent to Gram-negative bacteria and therefore, systemic administration of a killed B. bronchiseptica vaccine may lead to endotoxic shock due to LPS. Accordingly, killed vaccines need to be highly purified to minimize the amount of LPS. Such purification makes the manufacture of the vaccine more complex, often leading to the loss of effective antigens, and thereby increasing the overall cost of production. Therefore, there remains a need to obtain a vaccine for systemic administration that is safe and efficacious against B. bronchiseptica. 
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